Nail fungal infections are a widespread and hard to cure affliction, and so are some other skin afflictions. While several systemic and topical treatments are commercially available, none is completely satisfactory, as evidenced by the continuous effort to find new therapeutic methods. The nail fungal infection known as onychomycosis, caused mainly by the dermatophyte trichphyton rubrum, is particularly difficult to treat, and while some treatments prove effective, there are significant side-effects and the infection is recurrent.
The most prominent drugs for nail fungal infections are terbinafine and ciclopirox. Other antifungal drugs in use or development include griseofulvin, posaconazole, amorolfine, itraconazole, econazole and butenafine.
Terbinafine (Lamisil®), a very effective drug for the treatment of onychomycosis (tinea unguium), is mainly administered systemically, despite the known side-effects like liver toxicity. Terbinafine is commercially available also as the 1% Lamisil® OTC topical cream, but the indications for the cream are different.
The significant side-effects are the main reason why topical treatments, likely to diminish the systemic effects, are being coveted, and attempts are being made to develop efficient topical drugs, with minimal side-effects.
The FDA www.ClinicalTrials.gov site lists 15 clinical studies with terbinafine, mostly topical treatments against onychomycosis, including terbinafine nail lacquer. Higher concentrations of terbinafine and alternative actives, like posaconazole and 5% amorolfine nail lacquer are being investigated as possible treatment for nail fungal infections, which evidences the fact that there is still an unmet medical need for safe and effective topical treatments of nail fungal infections. Only four clinical studies are listed on this site for ciclopirox, out of which none for onychomycosis or other nail infections, which shows that ciclopirox is not considered a preferred treatment, while terbinafine is.
Another antifungal drug, ciclopirox, of limited antifungal activity, is administered only topically. The commercial product Penlac® nail lacquer is a 8% ciclopirox topical solution which is applied once daily and repeatedly to the nail and to the skin beneath it to form a lacquer layer. Another commercial nail lacquer is 5% amorolfine, commercially available as OTC in the UK as Loceryl or Curanail.
The nail application of Penlac® results in formation of a dry film, after evaporation of the liquid components of the composition. Penlac® composition includes the following ingredients: each gram of PENLAC® NAIL LACQUER (ciclopirox) Topical Solution, 8%, contains 80 mg ciclopirox in a solution base consisting of ethyl acetate, NF; isopropyl alcohol, USP; and butyl monoester of poly[methylvinyl ether/maleic acid] in isopropyl alcohol. Ethyl acetate and isopropyl alcohol are solvents that vaporize after application.
The activity of the topical lacquers like Penlac® depends in large measure on the composition of the film that forms on the nail after the evaporation of the solvents. In the Penlac® case, after the evaporation of the solvents, the film is formed by ciclopirox in butyl monoester of poly[methylvinyl ether/maleic acid (Gantrez® ES-435), a copolymer.
Conventional antifungal compositions, however, exhibit poor to marginal efficacy against nail fungal infections, and there is clearly an unmet need for antifungal compositions with improved efficacy in the treatment of nail fungal infections.